DESCRIPTION: This proposal centers on understanding the function of the 14-3-3 signaling molecule. The major goal is to establish that 14-3-3 specifically binds to serine-phosphorylated proteins and helps to assemble signaling complexes that regulate cell proliferation, differentiation, and cell motility. This hypothesis will be tested through three specific experimental aims. The first will be to assess the ability of 14-3-3 to bind to specific phosphoserine motifs in vivo (through the use of mutant forms of the Raf-1 kinase). The second aim focuses on examining the role of 14-3-3 in Raf-1-mediated signal transduction through an analysis of the effects of specific 14-3-3 inhibitors on Xenopus laevis embryo development. The third aim will then center on examining the role of 14-3-3 in the regulation of acting polymerization and cell motility in cultured fibroblasts. The expectation is that the results of these experiments will establish the importance of the 14-3-3 signaling molecules in cell growth regulation and development.